Unless stated otherwise, as used herein, the terms "arylalkylamine", "arylalkanolamine", "arylisonitrosoalkanone" and "acetophenone" shall mean an unsubstituted or substituted arylalkylamine, arylalkanolamine, arylisonitrosoalkanone and acetophenone, respectively.
Arylalkylamines are well known compounds which are useful and important chemical intermediates. They are used in the preparation of pharmacologically active compounds and, in some instances, are themselves pharmacologically active. For example, phenethylamine and hydroxyphenethylamine (tyramine) have sympathomimetic (adrenergic) action. Tyramine also is a moiety in opiates, and is useful as an intermediate or substituent in the preparation of other physiologically active compounds or compositions. Hydroxyltyramine (dopamine) is a physiologically important neural inhibitory transmitter.
U.S. Pat. No. 5,041,609 discloses a method of preparing arylalkylamines. An arylalkylketone is reacted with a lower alkyl nitrite in the presence of hydrogen chloride in a dipolar aprotic solvent to produce a reaction mixture which includes an aryl-.alpha.-oximinoalkyl ketone. Water is added to the mixture and the aryl-.alpha.-oximinoalkyl ketone is extracted from the aqueous reaction mixture with an organic solvent to produce a water free solution of the aryl-.alpha.-oximinoalkyl ketone. The water free solution is combined with a supported metal hydrogenation catalyst, a carboxylic acid and a strong inorganic acid. Then, hydrogen is added to produce a salt of the strong acid and an arylalkylamine derived from the aryl-.alpha.-oximinoalkyl amine.
U.S. Pat. application Ser. No. 07/630,127, now abandoned, discloses a method for the preparation of the ammonium salt of an arylalkylamine. An aryl-.alpha.-oximinoalkyl ketone is reacted with hydrogen in an aqueous reaction medium comprising hydrochloric acid and a noble metal catalyst to produce a reaction product comprising the salt of an arylalkylamine as its major component.
U.S. Pat. application Ser. No. 07/698,504 discloses a method of preparing an arylalkanolamine by hydrogenating an arylisonitrosoalkanone in the presence of a supported noble metal catalyst in a reaction medium comprising a weak carboxylic acid. The arylalkanolamine is obtained in the amine acylate salt form thereof which can then be converted to the hydrochloride salt thereof by reacting the same with hydrogen chloride in a reaction medium comprising an alkyl alcohol.
Tyramine is described in the literature as produced by the sodium in ethanol reduction of p-hydroxyphenylmethylcyanate, J. Chem. Soc. v. 9:5, p. 1127 (1909); by the platinum catalyzed hydrogenation of p-hydroxyphenylmethylcyanate, Buck, J.S., J. Am. Chem. Soc. v. 55, p. 3389 (1933); and by a lactobacillus decarboxylation of 1-(p-hydroxyphenyl)-2-aminopropionic acid, Umezi, M. et al., Hakko Kogaku Kaishi v. 55(2), pp. 68-74 (1977). Other roots for obtaining phenylethylamines via reduction of either vinyl nitro groups, N-N-dibenzylamino groups, or alkylcyanides are known. The reagents used are hydrazine, NaBH.sub.4 and hydrogen over platinum.
One disadvantage of some or all of the above processes is that the starting materials are waste intensive, unsafe, and expensive. Another disadvantage is the conversion rates are not very high. Still another disadvantage is that they require the use of large amounts of catalysts.
U.S. Pat. Nos. 1,995,709 ("U.S. Pat. No. '709") and 2,517,906 ("U.S. Pat. No. '906") disclose -a multi-operations procedure for the preparation of substituted phenyl propanol amines, and, more particularly, the preparation of 1-(p- or m-hydroxyphenyl)-2-amino-1-propanol (in U.S. Pat. No. '709), and 1-(p-aminophenyl)-2-amino-1-propanol (in U.S. Pat. No. '906). In U.S. Pat. No. '709, p- or m-hydroxypropiophenone is reacted with a lower alkyl nitrite in ether in the presence of hydrogen chloride to produce p- or m-hydroxyisonitrosopropiophenone, which then is separated from the reaction mixture by alkaline extraction and recovered from the alkaline solution by precipitation induced by acidification of the extract, after which the precipitate is recrystallized. The p- or m-hydroxyisonitrosopropiophenone thus separated is then reacted with hydrogen in the presence of palladium on charcoal in absolute alcohol containing dry hydrogen chloride until reduction stops, after which the amino ketone is recovered as a filtrate. The filtrate is dried and purified by recrystallization. Then, the amino ketone is dissolved in water and reacted with hydrogen in the presence of palladium on charcoal. The reaction product is recovered as the hydrochloride of the amino alcohol, for example, the hydrochloride of 1-(p-hydroxyphenyl)-2-aminopropanol (in U.S. Pat. No. No. '709) and the hydrochloride of 1-p-aminophenyl)-2-aminopropanol (in U.S. Pat. No. '906).
U.S. Pat. No. No. 2,505,645 employs the acidic catalytic hydrogenation process described in U.S. Pat. No. '709 and U.S. Pat. No. '906 in a method of preparing .alpha.-phenyl-.beta.-hydroxyphenyl-.beta.-hydroxyethylamine. U.S. Pat. No. No. 2,784,228 describes a partially aqueous process for the catalytic reduction of .alpha.-oximino ketones using alkaline solutions instead of acidic solutions to obtain a desired amino alcohol.
U.S. Pat. No. No. 3,028,429 describes a process for the hydrogenation of isonitrosopropiophenone to produce 1-phenyl-2-aminopropanol. The process is a modification claimed to improve the yields of the general process described in U.S. Pat. No. '709 and U.S. Pat. No. '906.
U.S. Pat. No. No. 3,966,813 discloses a process for preparation of 1-p-hydroxyphenyl)-2-aminoethanol, otherwise referred to as octopamine, by reacting a hydroxyacetophenone with a lower alkyl nitrite in a dipolar aprotic solvent in the presence of a hydrogen chloride catalyst to form isonitrosoacetophenone, and, then, catalytically hydrogenating the isonitrosoacetophenone in the presence of palladium to reduce the isonitroso- and keto- moieties on the isonitroso-acetophenone molecule. The dipolar aprotic solvent is relatively expensive. The yields are about 70 to 80 percent. That patent provides several examples for the preparation of both m-hydroxyisonitrosoacetophenone and p-hydroxyisonitrosoacetophenone. Example 4 describes the hydrogenation step for the conversion of a hydroxyisonitrosoacetophenone to a 1-(hydroxy-phenyl)-2-aminoethanol. That example pertains to hydrogenation of the meta-substituted hydroxyisonitrosoacetophenone.
The present invention discloses improved methods for the preparation of arylalkylamines from corresponding arylisonitrosoalkanones and acetophenones. The methods involve fewer steps for the addition of reactants, avoid the use of toxic materials and complicated extraction procedures, and result in higher conversions than the prior methods.
These and other advantages and objects of the present invention will become apparent from the following description.